Stent with embedded material

ABSTRACT

An endoprosthesis such as a stent is composed of a metal or ceramic, such as Irox, embedded in the stent material.

TECHNICAL FIELD

This disclosure relates to stents with embedded material.

BACKGROUND

The body includes various passageways such as arteries, other bloodvessels, and other body lumens. These passageways sometimes becomeoccluded or weakened. For example, the passageways can be occluded by atumor, restricted by plaque, or weakened by an aneurysm. When thisoccurs, the passageway can be reopened or reinforced with a medicalendoprosthesis. An endoprosthesis is typically a tubular member that isplaced in a lumen in the body. Examples of endoprostheses includestents, covered stents, and stent-grafts.

Endoprostheses can be delivered inside the body by a catheter thatsupports the endoprosthesis in a compacted or reduced-size form as theendoprosthesis is transported to a desired site. Upon reaching the site,the endoprosthesis is expanded, e.g., so that it can contact the wallsof the lumen. Stent delivery is further discussed in Heath, U.S. Pat.No. 6,290,721, the entire contents of which is hereby incorporated byreference herein.

The expansion mechanism may include forcing the endoprosthesis to expandradially. For example, the expansion mechanism can include the cathetercarrying a balloon, which carries a balloon-expandable endoprosthesis.The balloon can be inflated to deform and to fix the expandedendoprosthesis at a predetermined position in contact with the lumenwall. The balloon can then be deflated, and the catheter withdrawn fromthe lumen.

SUMMARY

In an aspect, the invention features an endoprosthesis including a metalhaving embedded therein a second metal or ceramic.

In another aspect, the invention features a method of adhering a ceramicto an endoprosthesis. The method includes embedding ceramic precursorparticles into the endoprosthesis wall, and converting the precursorparticles to ceramic.

Embodiments may also include one or more of the following features. Thesecond metal or ceramic can be exposed at the surface of theendoprosthesis metal. The second metal or ceramic can be embedded to adepth of about one micron or less. The endoprosthesis can include awall, and the second metal or ceramic can be embedded to a depth ofabout 1% or less of the thickness of the wall. The wall can be formedsubstantially of a single metal layer. The second metal or ceramic canbe alloyed with the endoprosthesis metal. The second metal can be in theform of particles having a size of about one micron or less. The secondmetal or ceramic can be embedded in discontinuous regions of about onemicron or less. The second metal can form a discontinuous coating on thesurface of the endoprosthesis. The second metal can be selected fromtitanium, zirconium, hafnium, niobium, tantalum, ruthenium, iridium, andplatinum. The ceramic can be an oxide. The ceramic can be Irox. Theendoprosthesis metal can be stainless steel, chrome, nitinol, cobalt,chromium, nickel, titanium, tungsten, tantalum, rhenium, iridium,silver, gold, bismuth, platinum, superelastic alloys, or other alloysthereof.

Embodiments may also include one or more of the following features. Theembedding can include melting the endoprosthesis wall to at leastpartially cover the precursor particles with the endoprosthesis wallmaterial. The melting can include heating with a laser. The laser can bea pulsed laser, an excimer laser, a YAG laser, or a continuous wavelaser. The embedding can include laser shock peening. The embedding caninclude embedding to a thickness of about 2 nm to 5 μm. The embeddingcan include alloying the precursor particles with the endoprosthesiswall. The converting can include oxidizing the precursor particles. Theoxidizing can include electrochemical oxidation. The electrochemicaloxidation can include cyclic voltammetry. The precursor particles can bedeposited onto the surface of the endoprosthesis. The precursorparticles can be deposited by sputtering, pulsed laser deposition, orchemical vapor deposition. The ceramic can be adhered on all exposedsurfaces of the endoprosthesis. The ceramic can be adhered only on theabluminal surfaces. The ceramic can be adhered only on the abluminal andcurface surfaces.

Embodiments may include one or more of the following advantages. Astent, e.g. made of metal, can be provided with another material, suchas a ceramic, e.g. iridium oxide (“Irox”), which can have beneficialtherapeutic effects, such as reducing restenosis and encouragingendothelialization. The ceramic can be provided on the surface such thatit is tightly adhered to the stent to reduce the likelihood that thematerial will be fractured, flake or otherwise be dislodged from thestent. The coverage or concentration of the material on the surface canbe controlled. The nature of the ceramic, such as the degree ofoxidation can be carefully controlled, e.g. using electrochemicaltechniques. The material can be provided as small particles, andembedded in the outer surface of the stent so as to not excessivelydegrade the mechanical properties of the metal. Adhering the material tothe stent and oxidizing the material can be performed in separate steps,which simplify processing and provide enhanced optimization. The oxidecan be adhered directly to the surface of the stent metal, without usingtie layers or abrasion unless desired.

Still further aspects, features, embodiments, and advantages follow.

DESCRIPTION OF DRAWINGS

FIGS. 1A-1C are longitudinal cross-sectional views illustrating deliveryof a stent in a collapsed state, expansion of the stent, and deploymentof the stent.

FIG. 2 is a perspective view of a stent.

FIG. 3 is a cross-sectional view of a stent wall showing metal particlesembedded in the surface.

FIGS. 4A-4D are cross-sectional views of a stent wall illustratingschematically application of a ceramic. FIG. 4A illustrates depositionof particles onto the surface. FIG. 4B illustrates embedding theparticles into the surface; FIG. 4C illustrates particles embedded inthe surface; FIG. 4D illustrates oxidation of the particles.

FIG. 5 is a schematic of a laser surface treatment system showing alaser system arranged to illuminate a stent in a chamber.

FIG. 6 is a schematic of an oxidation apparatus.

FIG. 7 is a cross-sectional view of a stent substrate showing particlesembedded with alloying.

FIG. 8 is a cross-sectional view of a stent substrate showing particlesembedded in a stent substrate that is highly irregular, with deepdivots, etc. as would occur with a pulsed laser.

DETAILED DESCRIPTION

Referring to FIGS. 1A-1C, a stent 20 is placed over a balloon 12 carriednear a distal end of a catheter 14, and is directed through the lumen 16(FIG. 1A) until the portion carry the balloon and stent reaches theregion of an occlusion 18. The stent 20 is then radially expanded byinflating the balloon 12 and compressed against the vessel wall with theresult that occlusion 18 is compressed, and the vessel wall surroundingit undergoes a radial expansion (FIG. 1B). The pressure is then releasedfrom the balloon and the catheter is withdrawn from the vessel (FIG.1C).

Referring to FIG. 2, the stent 20 includes a plurality of fenestrations22 defined in a wall 23. Stent 22 includes several surface regions,including an outer, or abluminal, surface 24, an inner, or luminal,surface 26, and a plurality of cutface surfaces 28. The stent can beballoon expandable, as illustrated above, or self-expanding stent.Examples of stents are described in Heath '721, incorporated supra.

Referring to FIG. 3, stent wall 23, shown in cross-sectional view,includes a body 30, e.g. a metal such as stainless steel. The bodyincludes stent surface 32, which may be any or all of the abluminal,luminal or cut surfaces, including a material, such as a ceramic, e.g.Irox, in the form of particles 50, 60. The material is embedded intothis surface and can include a plurality of exposed particles 50 andburied particles 60. The embedded material is tightly adhered to thestent material, which reduces the likelihood that the material will bedislodged while the stent is in use. The material is embedded in thesurface of the stent wall to a thickness of T₉₀, which is preferably asmall percentage of the overall wall thickness, so that the presence ofthe material does not degrade the mechanical properties of the stent.

Referring to FIGS. 4A-4D, the material can be embedded by depositing aceramic precursor metal onto the stent, melting a surface layer of thestent, cooling the stent, and then oxidizing the precursor metal to formthe ceramic. Referring particularly to FIG. 4A, ceramic precursorparticles 40 are deposited on stent surface 32 by e.g. physical vapordeposition. Referring particularly to FIG. 4B, the precursor is embeddedby melting the surface of the stent metal, e.g. with a laser. Laserirradiation 36 causes localized melting to a thickness T₉₂ (whichsubstantially corresponds to thickness T₉₀). As the surface becomes softor a liquid, particles are surrounded or partially surrounded by thestent metal. Referring to FIG. 4C, the surface is then allowed to cool,solidifying the stent metal about the precursor metal, and tightlyadhering the precursor to the stent metal. Referring to FIG. 4D, theparticles are then oxidized, e.g. in an electrochemical cell, to providean embedded ceramic. Particles that are exposed 50 have been oxidized toproduce regions of oxide 52.

Referring to FIG. 5, localized melting can be performed with a lasersystem 68, including an irradiation chamber 70 containing stent 20 heldin place by a moveable clip 74 resting on a base 72, and a laser 76. Thechamber 70 may be under vacuum, filled with an inert gas, or filled witha liquid. In one embodiment, chamber 70 may be under vacuum or filledwith an inert gas so that irradiation of stent 20 by laser light causeslocal melting of stent wall, allowing particles to embed into thesurface of stent wall. In another embodiment, chamber 70 may be filledwith water so that irradiation of stent 20 by laser light effects lasershock peening at the stent surface, embedding particles into the stentwall. Chamber 70 may be made of any suitable material, optionallycontaining a window 78 allowing passage of laser light into the chamber.In an alternative embodiment, laser 76 may be located inside chamber 70.

In embodiments, sufficient laser energy is provided to melt the stentmetal surface to a thickness T₉₂, which is about 5% or less, e.g. about1% to 0.1% of the overall thickness of the stent metal. The thickness ofthe melted regions may be about 5% or more of the particle diameter,e.g. about 25 to 200% of the particle diameter. In embodiments, thethickness of the melted region is about 5 nm to about 2 microns, e.g. 10nm to 500 nm. In particular embodiments, the laser energy is sufficientto melt the stent metal but not to melt the ceramic precursor metal.Stainless steel, for example, has a lower melting temperature thaniridium. In other embodiments, the laser energy is sufficient to causemelting or partial melting of both the precursor metal and stent metal,which can lead to alloying between the precursor and stent metal, whichcan enhance adherence. Laser alloying is further described in I. Mannaet. al., Micro-Structural Evaluation of Laser Surface Alloying of Tiwith Ir, Scripta Materialia 37(5) 561 (1997) and C. Tassin et. al.,Improvement of the Wear Resistance of 316 L Stainless Steel by LaserSurface Alloying, Surface and Coating Technology 80(9), 207 (1996), theentire disclosure of each of which is hereby incorporated by referenceherein. Alloying can reduce the sharpness of the discontinuity betweenthe stent metal and the precursor alloy. The composition of the alloycan be graduated from pure stent metal to pure precursor metal, whichenhances adhesion, and reduces the likelihood of dislodgement, e.g. asthe stent is flexed in use. Suitable lasers include continuous wave orpulsed lasers. Suitable continuous wave lasers include CO2 lasers.Suitable pulsed lasers include excimer lasers operating in the UV, orYAG lasers. A particular laser is a UV laser operating at a wavelengthof 193 nm and a fluence of 300 mj/cm² or greater. In other embodiments,the precursor metal can be embedded by techniques such as physicalacceleration of the precursor particles into the surface of the stentmetal, e.g. by kinetic spraying or laser shock peening. Spraying andlaser shock peening methods are further discussed in U.S. Patent Pub.No. 2005/0182478 and U.S. Patent Pub. No. 2009/0118815, the entiredisclosure of each of which is incorporated herein by reference.

Referring to FIG. 6, a system 78 for electrochemically oxidizing theprecursor particles to ceramic includes a potentiostat 80, a referenceelectrode 82, a counter electrode 84, and stent 20 coated with precursorparticles, each immersed in bath 86 filled with an electrolyte solution.In embodiments, the precursor metal is converted to oxide, i.e. ceramic,using cyclic voltammetry or other electrochemical techniques. In oneembodiment, cyclic voltammetry can be carried out utilizing anelectrolyte solution such as a physiologic phosphate buffered salinesolution. The degree of oxidation can be controlled by altering theelectrochemical parameters, for example, the ranges of electrochemicalpotential and the number of cycles. In embodiments, the metal to oxygenratio can range from about 1:1 to 1:2. Oxidation utilizing cyclicvoltammetry and characterization of oxidized materials is furtherdiscussed in I. S. Lee et. al., Biocompatibility and Charge InjectionProperty of Iridium Film Formed by Ion Beam Assisted Deposition,Biomaterials 24, 2225 (2003); E. A. Irhayem et. al., Glucose DetectionBased on Electrochemically Formed Ir Oxide Films, J. ElectroanalyticalChem. 538, 153 (2002); and R. A. Silva et. al., ElectrochemicalCharacterization of Oxide Films Formed on Ti-6Al-4V Alloy Implanted withIr for Bioengineering Applications, Electrochemica Acta 43(102), 203(1998), the entire disclosure of each of which is hereby incorporated byreference herein. The surface of the medical device, e.g. of stainlesssteel, can be passivated during the electrolyte process. In embodiments,a drug is provided in the electrolyte such that it is incorporated intothe particles during oxidation.

In embodiments, the ceramic precursor metal is a pure metal or an alloysuch as titanium, zirconium, hafnium, niobium, tantalum, ruthenium,rhodium, iridium, platinum, and their alloys. Suitable ceramics includemetal oxides and nitrides. Particular oxides provide therapeuticeffects, such as enhancing endothelialization. A particular oxide isiridium oxide (Irox), which is further discussed in U.S. Pat. No.5,980,566 and U.S. Pat. No. 7,713,297. The precursor metal is preferablydeposited in particulate form. For example, the particles can have adiameter that is small compared to the stent wall thickness, e.g. about10% or less, e.g. 0.1 to 1% of the thickness or less. In embodiments,the particles have a diameter in the nanometer range to micron range,e.g. 1 nm to about 1 micron, e.g. 200 nm to 700 nm. The particles aredistributed such that they substantially cover a surface such as theabluminal surface, or partially cover the surface, e.g. 50% or less ofthe surface, leaving a desired pattern of the surface area exposed. Inembodiments, the density of the particles on the surface is such thatthe entire surface is covered. In other embodiments, the density of theparticles is such that discrete regions are covered, with exposed stentmetal between the regions. The distance between regions can be, e.g.about 1 μm or less. The particles can be deposited by sputteringtechniques such as physical vapor deposition (PVD) and pulsed laserdeposition (PLD), or by electrostatic or electrochemical deposition.Suitable PVD deposition techniques are described in X. Yan et. al., NewMOCVD Precursor for Iridium Thin Films Deposition, Materials Letters 61,216-218 (2007); U. Helmersson et. al., Ionized Physical Vapor Deposition(IPVD): A Review of Technology and Applications, Thin Solid Films 513,1-24 (2006); and J. Singh and D. E. Wolfe, Review: Nano andMacro-Structured Component Fabrication by Electron Beam-Physical VaporDeposition (EB-PVD), Journal of Materials Science, 40, 1-26 (2005), U.S.Patent Pub. No. 2008/0294236, and U.S. Patent Pub. No. 2008/0294246, theentire disclosure of each of which is incorporated herein by reference.

In embodiments, the stent metal can be stainless steel, chrome, nickel,cobalt, tantalum, superelastic alloys such as nitiniol, cobalt chromium,MP35N, and other metals. Suitable stent materials and stent designs aredescribed in Heath '721, supra. In embodiments, the stent can include anouter layer of a different metal into which the precursor alloy isembedded, e.g. a titanium layer on a stent body formed of 316 stainlesssteel. A particular advantage of other embodiments is that the precursorparticles can be embedded directly into a superficial region of thestent metal without treatment of the stent, such as the deposition of aseparate metal layer or roughening the surface

In one embodiment, ceramic is adhered only on the abluminal surface ofthe stent. This construction may be accomplished by, e.g. coatingprecursor particles on a stent material before forming thefenestrations. In another embodiment, ceramic is adhered only onabluminal and cutface surfaces of the stent. This construction may beaccomplished by, e.g., coating precursor particles on a stent containinga mandrel, which shields the luminal surfaces from deposition byprecursor particles. In each of these embodiments, the stent may thentreated with a laser to embed the precursor particles, and the precursorparticles may then be oxidized to form regions of embedded ceramic onlyon the abluminal and/or cutface surfaces.

Referring to FIG. 7, in embodiments, precursor particles 50 (and 60) areembedded into the surface, such that regions 54 (and 64) of theinterface of the particles and the stent metal are composed of a matrixof the precursor and stent metal, such as an alloy. An alloy is formedby heating to a temperature sufficient to melt both the stent and theparticles. The alloying can be performed simultaneously with embeddingthe particles by heating the particles above their melting point.Alternatively, embedding and alloying can be performed sequentially. Forexample, in a first step particles can be embedded, e.g. by heating to atemperature above the stent metal melting point but below the particlemetal melting point. In a subsequent step, the embedded assembly isheated above the melting point of the particles and stent metal to causeco-melting and mixing. In embodiments, only a portion of the particlesare alloyed with adjacent stent metal. In other embodiments,substantially the entire particle is alloyed with the stent metal,providing a domain of alloyed metal. In embodiments, the particles canbe coated or partially coated with a second metal. The second metal canfacilitate alloying. For example, the second meal can be selected tohave a melting temperature that is below the melting temperature of theprimary metal of the particle to facilitate co-melting with the stentmetal without melting the primary metal of the particle. The secondmetal can be selected for its capacity to form a desired alloy with thestent metal or the primary particle metal to provide desirablemechanical properties.

Referring to FIG. 8, in embodiments, the morphology, roughness orporosity of the stent surface is controlled. A stent surface 36 isroughened to contain pits, grooves, and other surface irregularities 90.Such surface may contain exposed embedded precursor particles 50 and/orburied embedded precursor particles 60. The stent may also contain voidspaces 92 which may be produced by regions of stent wall 30, by regionsof precursor particles, or by some combination thereof. A functionalmolecule, e.g. an organic, drug, polymer, protein, DNA, and similarmaterial can be incorporated into groves, pits, void spaces, and otherfeatures of the roughened stent surface. Suitable functional moleculesinclude D-Phe-Pro-Arg chloromethyl ketone, an RGD peptide-containingcompound, heparin, hirudin, antithrombin compounds, platelet receptorantagonists, anti-thrombin antibodies, anti-platelet receptorantibodies, aspirin, paclitaxel, prostaglandin inhibitors, plateletinhibitors and tick antiplatelet peptides. Such molecules are furtherdescribed in U.S. Pub. No. 2005/0251249, the entire disclosure of whichis incorporated herein by reference. In other embodiments, a drugcontaining polymer layer can be applied to the surface containingembedded particles. The adhesion of the polymer can be enhanced by theroughened surface. In other embodiments, embedding the particles asdescribed above provides sufficient roughness without the formation ofpits and grooves. Suitable polymers and drugs are described in U.S.Patent Pub. Nos. 2008/0294236 and 2008/0294246.

The roughened surface can be formed during or after the particles areembedded or formed in the ceramic. In embodiments, the roughened surfaceis formed using a pulsed laser, e.g. an excimer laser. The shots fromthe laser can form divots in the surface. The size, depth and number ofdivots can be controlled by controlling the wavelength, fluence, pulsewidth, number of pulses, and location of pulses. The divots can beformed simultaneously while embedding the particles. Alternatively, thedivots can be formed before or subsequently to embedding the particles.In other embodiments, the surface is roughened by other techniques, e.g.by etching, mechanical bombardment or laser shock peening technique. Inembodiments, the porosity formed by laser techniques can be controlled,e.g. decreased, by subsequently short peen treatment of the surface toclose divots. The divots can be formed on part or all of the stentsurfaces. The divots can be formed in a pattern, e.g. lines runningalong the stent axis. In embodiments, the depth of the divots is e.g.five times or less than the particle size, e.g. about 0.5 to twice theparticle size. In embodiments, the depth of the divots is about 5μ orless, e.g. 0.5 to 2 microns.

As discussed above, particles can be deposited as a precursor metalwhich is subsequently oxidized. An advantage of this technique is thatexposure of the oxide to high temperature such as melting temperaturesat which the oxide can degrade can be minimized. In other embodiments,oxide particles can be deposited directly, e.g. by oxidizing metalduring PVD. An advantage of this technique is that an oxidation stepafter embedding may not be performed. In embodiments, embedding can beperformed during particle deposition, e.g. by focusing laser energy onthe deposited surface during PVD. The laser illumination can be variedto embed particles at desired locations. Nonembedded particles can beremoved by washing.

The process can be performed on a stent precursor, e.g. base metal tubeor the stent. In other embodiments, particles are embedded by depositingthe particles as to a metal precursor tube, and then drawing the tube tosmaller diameters to forge the particles into the stent metal. A maskcan be used to prevent depositing at undesired locations. For example, amandrel can be used to shield the interior of the stent. The process canbe used with other endoprostheses or medical devices, such as catheters,guide wires, and filters.

All publications, patent applications, and patents cited above areincorporated by references herein in their entirety.

Still other embodiments are in the following claims.

1. An endoprosthesis comprising a metal wall having embedded thereinmetal or ceramic particles, the particles comprising a first materialalloyed with the metal wall and a second, different materialsubstantially unalloyed with the metal wall.
 2. The endoprosthesis ofclaim 1 wherein at least some of the metal or ceramic particles areexposed at a surface of the endoprosthesis metal wall.
 3. Theendoprosthesis of claim 1 wherein the metal or ceramic particles areembedded to a depth of about one micron or less.
 4. The endoprosthesisof claim 1 wherein the metal or ceramic particles are embedded to adepth of about 1% or less of the thickness of the metal wall.
 5. Theendoprosthesis of claim 4 wherein the metal wall is formed substantiallyof a single metal layer.
 6. The endoprosthesis of claim 1 wherein themetal or ceramic particles have a particle size of about one micron orless.
 7. The endoprosthesis of claim 1 wherein the metal or ceramicparticles are embedded in discontinuous regions of about one micron orless.
 8. The endoprosthesis of claim 1 wherein the metal or ceramicparticles form a discontinuous coating on a surface of theendoprosthesis.
 9. The endoprosthesis of claim 1 wherein the metalparticles comprises a metal selected from titanium, zirconium, hafnium,niobium, tantalum, ruthenium, iridium, and platinum.
 10. Theendoprosthesis of claim 1 wherein the ceramic particles comprise anoxide.
 11. The endoprosthesis of claim 1 wherein in the ceramicparticles comprise Irox.
 12. The endoprosthesis of claim 1 wherein theendoprosthesis metal is selected from stainless steel, chrome, nitinol,cobalt chromium, nickel, titanium, tungsten, tantalum, rhenium, iridium,silver, gold, bismuth, platinum, supereleastic alloys, and other alloysthereof.
 13. The endoprosthesis of claim 1 wherein the first materialhas a melting temperature lower than a melting temperature of the secondmaterial.
 14. The endoprosthesis of claim 13 wherein the meltingtemperature of the first material is lower than a melting temperature ofthe metal wall and the melting temperature of the second material ishigher than the melting temperature of the metal wall.
 15. Theendoprosthesis of claim 1 wherein the first material is coated on thesecond material.
 16. The endoprosthesis of claim 1 wherein the firstmaterial and the metal wall are alloyed by co-melting the first materialand the metal wall.